Role of Oxygen Metabolite in the Oxygen Paradox in Hypoxic Myocardium

Abstract

The study was conducted to confirm the hypothesis that cytotoxic oxygen free radicals are involved in myocardial cellular damage upon reoxygenation of hypoxic hearts(oxygen paradox), and to identify which species of oxygen radicals might be responsible for the damage. Oxygen paradox was induced in isolated, Langendorff preparations of rat heart by hypoxic, cardioplegic perfusion(90 min) followed by oxygen-repleted perfusion(20 min). The releases of cytosolic enzymes(creatine phosphokinase, CPK: lactic dehydrogenase, LDH) and a lipid peroxidation product, malondialdehyde (MDA) into the coronary effluent were assayed as the indicators of myocardial cellular damage. To confirm the generation of oxygen radicals during the process of oxygen paradox, HzOz relaesed into the coronary effluent was detected using a fluorescent dichlorofluorescln. assay. The releases of CPK, LDH and MOA into the coronary effluent were abruptly increased by reoxygenation in isolated hypoxic rat hearts. The concentration of HzOz detected in the coronary effluent was also markedly elevated upon reoxygenation. The increases of enzymes and a lipid peroxidation product were prevented to various degrees by scavengers of O2 (superoxide dismutase, 500, 10,000 U), HzOz (catalase, 25,000 U) and OH· (dimethylsulfoxide, DMSO, 10%), and by an iron-chelator deferoxamine (0.5 mM). HzOz in the coronary effluent increased dramatically with the adminstration of SOD in the perfusion solutions, while it was never detected when catalase was given. It was concluded from these results that the generation of oxygen free radicals increased during the process of oxygen paradox in hypoxic hearts, and that the hydroxyl radical might play a major contributing role in the development of the myocardial cellular damage through the lipid peroxidation of cell membranes.